POS0120 NEUROLOGICAL INVOLVEMENT IN A MONOCENTRIC COHORT OF PATIENTS WITH SERONEGATIVE ANTIPHOSPHOLIPID SYNDROME
Authors: L. Rapino, S. Truglia, S. Mancuso, M. De Michele, D. Toni, I. Berto, M. Sorice, R. Misasi, A. Capozzi, C. Alessandri, F. Conti
Journal: Annals of the Rheumatic Diseases (2022)

Background The nervous system is affected in a relevant number of patients with antiphospholipid syndrome (APS), being responsible for high morbidity and mortality rates. The identification of neurological manifestations is crucial since those symptoms may benefit from anticoagulation treatment. Noteworthy, the prevalence and the characteristics of neurological manifestations in the subset of patients with “seronegative APS” (SN-APS) still need to be investigated. Objectives The aim of this study was to assess the neurological involvement in patients with SN-APS. Secondly, association between non-conventional antiphospholipid antibodies (aPL) and clinical characteristics were investigated. Methods We included all consecutive patients referred to the Lupus Clinic and to the Stroke Unit of our Hospital, presenting clinical features consistent with a diagnosis of APS despite the evidence of persistently negative tests for anti-cardiolipin antibodies (aCL), anti-β2 glycoprotein I, and lupus anticoagulant. Patients with an identified cause of thrombosis and/or pregnancy morbidity were excluded. Patients’ sera were analyzed for the detection of aCL using thin layer chromatography (TLC), while ELISA test was used to detect antibodies directed against the anti-vimentin/cardiolipin complex (aVim/CL). Results From January 2015 to October 2019, 40 patients with SN-APS and neurological involvement were enrolled. Clinical and demographic characteristics are reported in Table 1. Thirty-three patients (82.5%) resulted positive for at least one non-conventional test (62.5% positive on two occasions) while 17.5% were negative. The occurrence of aCL by TLC immunostaining was 33/40 (82.5%), while a Vim/CL were found in 10/40 (25%). Double positivity for aCL by TLC-immunostaining and aVim/CL was observed in 8/40 patients (20%). Patients who tested positive for non-conventional aPL on two occasions had a five-fold increased risk of developing venous thrombosis (LR 5.24; p=0.022). The positivity for aCL by TLC immunostaining determined an augmented risk of sinus vein thrombosis (LR 5.49; p=0.019) while positivity for aVim/CL raised the likelihood of epilepsy (LR 4.133; p=0.042). Almost all (16/18, 88%) patients with ischemic stroke resulted positive at least one test, 15 tested positive for aCL by TLC-immunostaining and 3 for aVim/CL. In this subset of patients, the positivity for non-conventional aPL on two occasions determined an increased risk of venous thrombosis (LR 8.905; p=0.003) and recurrent stroke (LR 6.321; p=0.012). In particular, those who tested positive for aVim/CL were at higher risk of developing recurrent stroke (LR 6.659; p=0.01). Table 1. Characteristics Patients N= 40 (%) Female/Male 35/5 Mean age in years (S.D. ) 48 (12.5) Thrombosis 34 (85) Arterial 23 (57.5) Venous 17 (42.5) Recurrent 13 (32.5) Pregnancy morbidity 12 (34.3) Recurrent miscarriage 11 (31.4) Foetal deaths 2 (5.7) Premature births 2 (5.7) Thrombosis + Pregnancy morbidity 6 (17.1) Neurological manifestations Stroke 18 (45) Recurrent stroke 7 (17.5) Transient ischemic attack 4 (10) Venous sinus thrombosis 5 (12.5) Headache 18 (45) Epilepsy 7 (17.5) Transverse myelitis 2 (5) Other manifestations Livedo reticularis 5 (12.5) Low platelets 3 (7.5) Conclusion The nervous system is one of the most frequently affected in APS, however only few data exist about prevalence, characteristics and outcome of its involvement in SN-APS patients. In this work, using TLC immunostaining and ELISA for aVim/CL, we identified non-conventional aPL antibodies in 62,5% SN-APS patients. This subset of patients presented a wide spectrum of neurological manifestations, with frequencies and features that resemble those observed in APS patients. Furthermore, we demonstrated the association between non-conventional aPL and neurological manifestations, such as sinus vein thrombosis, recurrent stroke and epilepsy. In conclusion, testing for non-conventional aPL antibodies may contribute to the evaluation of the stratification of risk for neurological manifestations in SN-APS. Disclosure of Interests None declared